PI3K-AKT, JAK2-STAT3 pathways and cell-cell contact regulate maspin subcellular localization.

Autor: Longhi MT; Instituto de Ciencias Biomedicas, Departamento de Biologia Celular e do Desenvolvimento, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil., Silva LE; Instituto de Ciencias Biomedicas, Departamento de Biologia Celular e do Desenvolvimento, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil., Pereira M; Instituto de Ciencias Biomedicas, Departamento de Biologia Celular e do Desenvolvimento, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil., Magalhães M; Instituto de Ciencias Biomedicas, Departamento de Biologia Celular e do Desenvolvimento, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil., Reina J; Instituto de Ciencias Biomedicas, Departamento de Biologia Celular e do Desenvolvimento, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil., Vitorino FNL; Laboratório de Ciclo Celular, Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, SP, 05503-900, Brazil., Gumbiner BM; Department of Pediatrics and Biochemistry, University of Washington School of Medicine, Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, 1900 9th Ave. Mailstop JMB-5, Seattle, WA, 98101, USA., da Cunha JPC; Laboratório de Ciclo Celular, Center of Toxins, Immune Response and Cell Signaling-CeTICS, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, SP, 05503-900, Brazil., Cella N; Instituto de Ciencias Biomedicas, Departamento de Biologia Celular e do Desenvolvimento, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP, 05508-000, Brazil. ncella@usp.br.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2021 Aug 14; Vol. 19 (1), pp. 86. Date of Electronic Publication: 2021 Aug 14.
DOI: 10.1186/s12964-021-00758-3
Abstrakt: Background: Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved in maspin nuclear localization and explored a possible role of cell-cell contact in this process.
Methods: MCF-10A cells were treated with pharmacological inhibitors against EGFR downstream pathways followed by EGF treatment. Maspin subcellular localization was determined by immunofluorescence. Proteomic and interactome analyses were conducted to identify maspin-binding proteins in EGF-treated cells only. To investigate the role of cell-cell contact these cells were either treated with chelating agents or plated on different cell densities. Maspin and E-cadherin subcellular localization was determined by immunofluorescence.
Results: We found that PI3K-Akt and JAK2-STAT3, but not MAP kinase pathway, regulate EGF-induced maspin nuclear accumulation in MCF-10A cells. We observed that maspin is predominantly nuclear in sparse cell culture, but it is redistributed to the cytoplasm in confluent cells even in the presence of EGF. Proteomic and interactome results suggest a role of maspin on post-transcriptional and translation regulation, protein folding and cell-cell adhesion.
Conclusions: Maspin nuclear accumulation is determined by an interplay between EGFR (via PI3K-Akt and JAK2-STAT3 pathways) and cell-cell contact. Video Abstract.
(© 2021. The Author(s).)
Databáze: MEDLINE
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